New insights into the influences of firework combustion on molecular composition and formation of sulfur- and halogen-containing organic compounds.

Firework (FW) events occur during various festivals worldwide and substantially negatively influence both air quality and human health. However, the effects of FWs on the chemical properties and formation of organic aerosols are far from clear. In this study, fine particulate matter (PM2.5) samples were collected in a suburban area in Qingdao, China during the Chinese Spring Festival. The concentrations of chemical species (especially carbonaceous components) in PM2.5 were measured using a combination of several state-of-the-art techniques. Our results showed that mass concentrations of water-soluble sulfate, potassium and chloride ions, and organic carbon drastically increased and became the predominant components in PM2.5 during FW events. Correspondingly, both the number and fractional contributions of sulfur (S)-containing subgroups (e.g., CHOS and CHONS compounds) and some chlorine (Cl)-containing organic (e.g., CHOSCl and CHONSCl) compounds identified using ultrahigh-resolution Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR MS) increased. The S- and Cl-containing compounds unique to the FW display period were identified, and their chemical characterization, sources, and formation mechanisms were elucidated by combining FT-ICR MS and quantum chemical calculations. Our results suggest that FW emissions play notable roles in both primary and secondary organic aerosol formation, especially for CHOS- and Cl-containing organic compounds.

Degradation of the emerging brominated flame retardant tetrabromobisphenol S using organo-montmorillonite supported nanoscale zero-valent iron.

The widespread occurrence of emerging brominated flame retardant tetrabromobisphenol S (TBBPS) has become a major environmental concern. In this study, a nanoscale zero-valent iron (nZVI) impregnated organic montmorillonite composite (nZVI-OMT) was successfully prepared and utilized to degrade TBBPS in aqueous solution. The results show that the nZVI-OMT composite was very stable and reusable as the nZVI was well dispersed on the organic montmorillonite. Organic montmorillonite clay layers provide a strong support, facilitate well dispersion of the nZVI chains, and accelerate the overall TBBPS transformation with a degradation rate constant 5.5 times higher than that of the original nZVI. Four major intermediates, including tribromobisphenol S (tri-BBPS), dibromobisphenol S (di-BBPS), bromobisphenol S (BBPS), and bisphenol S (BPS), were detected by high-resolution mass spectrometry (HRMS), indicating sequential reductive debromination of TBBPS mediated by nZVI-OMT. The effective elimination of acute ecotoxicity predicted by toxicity analysis also suggests that the debromination process is a safe and viable option for the treatment of TBBPS. Our results have shown for the first time that TBBPS can be rapidly degraded by an nZVI-OMT composite, expanding the potential use of clay-supported nZVI composites as an environmentally friendly material for wastewater treatment and groundwater remediation.

[Differences of Three Methods in Determining Ozone Sensitivity in Nanjing].

In recent years， ozone （O3） has become an increasingly important air pollutant in China. Identifying the sensitivity of O3 to the precursors volatile organic compounds （VOCs） and nitrogen oxides （NOx） can help make effective abatement strategies. This study compared three methods for determining O3-VOCs-NOx sensitivity： simulated photochemical indicator values and sensitivity coefficients derived from a three-dimensional air quality model and an observation-based model （OBM）， with a case study involving an O3 pollution event that occurred in Nanjing in late July 2017. The results showed that O3 sensitivity based on the photochemical indicator and sensitivity coefficients demonstrated similar spatial variations （over 50% of the grid cells of Nanjing exhibiting identical O3 sensitivity）. However， sensitivity coefficients identified a larger number of areas within a transitional O3 sensitivity regime， as opposed to the VOCs- or NOx-limited regime identified by the photochemical indicator. The determination of the latter was affected by the adopted threshold values. The OBM relied on the quality of the observational data. For example， positive biases in observed NO2 could lead to an underestimation of O3 sensitivity to NOx with the OBM. During the high pollution period， the three methods exhibited significant disparities. The photochemical indicator tended to suggest the VOCs-limited condition， whereas the OBM and sensitivity coefficients indicated the NOx-limited or transitional regimes.

Size-resolved light-absorbing organic carbon and organic molecular markers in Nanjing, east China: Seasonal variations and sources.

Owing to the potential influence of light-absorbing organic carbon (OC), also termed "brown carbon" (BrC), on the planetary radiation budget, many studies have focused on its absorption in single-sized ranges of particulate matter (PM). However, the size distribution and organic tracer-based source apportionment of BrC absorption have not been extensively investigated. In this study, size-resolved PM samples were collected using multi-stage impactors from eastern Nanjing during each season in 2017. The light absorption of methanol-extractable OC at 365 nm (Abs365, Mm-1) was determined using spectrophotometry, and a series of organic molecular markers (OMMs) was measured using a gas chromatography-mass spectrometer. Fine PM with an aerodynamic diameter <2.1 µm (PM2.1) dominated Abs365 (79.8 ± 10.4%) of the total size ranges with maxima and minima in winter and summer, respectively. The distributions of Abs365 shifted to larger PM sizes from winter to spring and summer due to lower primary emissions and increased BrC chromophores in dust. Except for low-volatility (po,*L < 10-10 atm) polycyclic aromatic hydrocarbons (PAHs), the non-polar OMMs, including n-alkanes, PAHs, oxygenated PAHs, and steranes, showed a bimodal distribution pattern. Secondary products of biogenic precursors and biomass burning tracers presented a unimodal distribution peaking at 0.4-0.7 µm, while sugar alcohols and saccharides were enriched in coarse PM. Their seasonal variations in average concentrations reflected intense photochemical reactions in summer, more biomass burning emissions in winter, and stronger microbial activity in spring and summer. Positive matrix factorization was used for the source apportionment of Abs365 in fine and coarse PM samples. Biomass burning contributed an average of 53.9% to the Abs365 of PM2.1 extracts. The Abs365 of coarse PM extracts was associated with various dust-related sources where the aging processes of aerosol organics could occur.

Characteristics of endoplasmic reticulum stress in colorectal cancer for predicting prognosis and developing treatment options.

BACKGROUND: An increasing body of evidence supports an essential role for endoplasmic reticulum stress (ERS) in colorectal cancer (CRC). In this study, we developed an ERS-related genes (ERSRGs) model to aid in the prognostic evaluation and treatment of CRC patients. METHODS: The training set and validation set data were extracted from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), respectively. ERSRGs were obtained from the GeneCards database. A prognostic risk scoring model was constructed using the least absolute shrinkage and selection operator (LASSO) along with univariate Cox regression analysis. To further predict the probability of survival for patients at 1, 2, and 3 years, a nomogram was devised. The advantages of the prognostic risk score model in screening patients' sensitive to chemotherapy and immunotherapy were analyzed by drug sensitivity analysis and immune correlation analysis. Finally, hub genes associated with poor prognosis in the risk model were screened by Protein-protein interaction (PPI) network and their expression was validated using clinical specimens. RESULTS: A risk model for overall survival (OS) was developed using 16 ERSRGs associated with prognosis. Through analyses, we demonstrated a high degree of reliability for the prognostic risk scoring model. The constructed nomograms performed well in predicting patient survival over 1, 3, and 5 years. The calibration curve and decision curve analysis (DCA) supported a high degree of accuracy for the model. Patients in the low-risk group had a lower IC50 for the common chemotherapy drug, 5-FU, and responded better to immunotherapy. hub poor prognostic genes were validated in CRC clinical specimens. CONCLUSION: We have identified and validated a new ERS prognostic marker that can accurately predict the survival status of CRC patients for clinicians and better provide personalized treatment plans.

[Seasonal Variations, Size Distributions, and Sources of Chemical Components of Submicron Particulate Matter in Nanjing].

Size-segregated particulate matter (PM) samples were collected in different seasons from 2016 to 2017 at the Xianlin Campus of Nanjing University. Mass concentrations of water-soluble inorganic ions, carbonaceous components, and elements were analyzed for PM with an aerodynamic diameter ≤ 1.1 µm (PM1.1; <0.4 µm, 0.4-0.7 µm, and 0.7-1.1 µm). The results showed that PM1.1, OC, NO3-, SO42-, and NH4+ exhibited higher ambient levels in fall-winter than those in spring-summer, which was attributed to the changes in local diffusion conditions, evaporation, and decomposition of non-refractory components. Elemental carbon (EC) reached its maximum concentration[(1.87±0.98) µg·m-3]in spring due to the increase in industrial and road dust resuspension. According to the characteristic ratio between bulk components, the anions in PM1.1 were dominated by NO3-, SO42-, and Cl- in Nanjing, and the carbonaceous components were mainly from fossil fuel combustions and associated aging processes. As the ambient temperature increased, the size distributions of thermo-unstable components including NH4+, NO3-, and OC shifted towards finer particles, whereas EC became more enriched in coarse particles, possibly due to the increase in emission intensity of motor vehicles and fugitive dust contributions. Since high relative humidity (>70%) is often accompanied by high temperature (>20℃) and improved diffusion conditions, a relative humidity of 60%-70% was more conducive to the formation of secondary inorganic ions in PM1.1. Source apportionment results based on the speciation data of PM1.1 showed that secondary formation processes[(66.6±18.3)%]and dust resuspension[(16.8±14.8)%]were the main contributors to PM1.1 in Nanjing, and further control of the emissions of gaseous precursors and dust is necessary.

[Variations in PM2.5 Composition and Sources During 2020-2021 COVID-19 Epidemic Periods in Nanjing].

To understand the changes in chemical composition and sources of PM2.5 under the extreme reduction background during the COVID-19 epidemic periods in Nanjing, hourly observation results of PM2.5 components (water-soluble inorganic ions, carbonaceous components, and inorganic elements) of two epidemic events from January to March 2020 and June to August 2021 were analyzed. In comparison to that during pre-epidemic periods, the concentration of NO3- during the two epidemic control periods decreased by 52.9% and 43.0%, respectively, which was larger than the decreases in NH4+(46.4% and 31.6%) and SO42-(33.8% and 16.5%). Since the observation site was located close to a main road, the decrease in elemental carbon (EC, 35.4% and 20.6%) was higher than that in organic carbon (OC, 11.1% and 16.2%). In reference to the variations in the characteristic ratios of the bulk components mentioned above, the epidemic control showed a more substantial influence on traffic emissions than industrial activities. The concentration time series of PM2.5 major components over the epidemic periods indicated that NOx from local traffic emissions had substantial contributions to the formation of NO3-, which led to local short-term PM2.5 pollution. In addition, the positive matrix factorization (PMF) model was used to analyze the hourly observation data of PM2.5 components. The seven identified factors were linked with metallurgy, firework and firecracker combustions, road traffic emissions, coal combustion, dust resuspension, secondary sulfate, and secondary nitrate. Because the nitrate was unstable under high temperature, the contribution of secondary nitrate to PM2.5 during the epidemic control period of 2021 (summer, 21.2%) was much lower than that during the epidemic control period of 2020 (winter, 60.6%); however, the formation of secondary components always dominated the contribution of PM2.5 sources. Therefore, emissions of NOx and SO2 should be further controlled to continuously reduce ambient PM2.5 concentrations in Chinese cities.

Towards Carbon Neutrality: Carbon Emission Performance of Science and Technology Finance Policy.

Combining technology with finance is the focus of supporting economic structure adjustment, and environmental benefits are also the proper meaning of the policy. Using the panel data of 274 cities in China from 2006 to 2017, this paper examines the impact of the Science and Technology Finance Policy (STFP) on carbon emission intensity in pilot cities and the transmission mechanisms through the difference-in-differences method and further explores the impact of STFP on the carbon emission intensity in neighboring cities. The results show that (1) STFP has significantly reduced carbon emission intensity in pilot cities and has dynamic effects, which gradually increase over time. There is significant heterogeneity in the carbon emission reduction effect of STFP, which produces stronger policy effects in first and second-tier cities and cities with higher information levels. (2) STFP achieves carbon emission reduction effects through three main pathways: the total factor productivity improvement effect, innovative elements agglomeration effect, and industrial structure optimization effect. (3) The STFP and national e-commerce demonstration policy have an interactive effect, and the two jointly contribute to the reduction in carbon emission intensity. From the perspective of a spatial effect, STFP has a radiation effect; that is, STFP not only reduces local carbon emission intensity but also curbs the carbon emission intensity in neighboring areas.

Evaluating the influence of constant source profile presumption on PMF analysis of PM2.5 by comparing long- and short-term hourly observation-based modeling.

Hourly PM2.5 speciation data have been widely used as an input of positive matrix factorization (PMF) model to apportion PM2.5 components to specific source-related factors. However, the influence of constant source profile presumption during the observation period is less investigated. In the current work, hourly concentrations of PM2.5 water-soluble inorganic ions, bulk organic and elemental carbon, and elements were obtained at an urban site in Nanjing, China from 2017 to 2020. PMF analysis based on observation data during specific pollution (firework combustion, sandstorm, and winter haze) and emission-reduction (COVID-19 pandemic) periods was compared with that using the whole 4-year data set (PMFwhole). Due to the lack of data variability, event-based PMF solutions did not separate secondary sulfate and nitrate. But they showed better performance in simulating average concentrations and temporal variations of input species, particularly for primary source markers, than the PMFwhole solution. After removing event data, PMF modeling was conducted for individual months (PMFmonth) and the 4-year period (PMF4-year), respectively. PMFmonth solutions reflected varied source profiles and contributions and reproduced monthly variations of input species better than the PMF4-year solution, but failed to capture seasonal patterns of secondary salts. Additionally, four winter pollution days were selected for hour-by-hour PMF simulations, and three sample sizes (500, 1000, and 2000) were tested using a moving window method. The results showed that using short-term observation data performed better in reflecting immediate changes in primary sources, which will benefit future air quality control when primary PM emissions begin to increase.

Inhibition of BTK improved APAP-induced liver injury via suppressing proinflammatory macrophages activation by restoring mitochondrion function.

BACKGROUND: Acetaminophen (APAP) overdose can cause severe liver injury and APAP-induced liver injury (AILI) is one of the leading causes of acute liver failure (ALF). Bruton's tyrosine kinase (BTK) is a key tyrosine kinase in immune responses, which plays an important role in many inflammatory diseases. However, its effect on AILI is still not clear. Here, we aimed to assess the effect of BTK on AILI and explore its underlying mechanism. METHODS: In our study, western blot and immunohistochemistry were used to detect the expression of BTK in AILI. The C57BL/6 mice were used to check the protective effect of BTK inhibition on AILI and the activation of BTK was confirmed in mice macrophages treated with APAP. Immunofluorescence, immunohistochemistry, oxygen consumption rate (OCR) detection, polymerase chain reaction (PCR), flow cytometry and western blot were used to determine the role of BTK in mitochondrial dynamics and function of macrophages and the underlying mechanisms in AILI. RESULTS: Our results showed that BTK upregulated in AILI. BTK inhibition protected mice from AILI and BTK was activated in mice macrophages in response to APAP. Mechanically, BTK inhibition promoted mitochondrial fusion and restored mitochondrial function through phospholipase C gamma 2 (PLCγ2)-reactive oxygen species (ROS)-Optic Atrophy 1(OPA1) pathway in macrophages and finally suppressed the release of proinflammatory cytokines. CONCLUSIONS: In conclusion, we found that BTK inhibition protected mice from AILI by restoring the mitochondrial function of macrophages through the improvement of the mitochondrial dynamic imbalance via PLCγ2-ROS-OPA1 signaling pathway, which indicated that BTK might be a potential therapeutic target of AILI.

Seasonal variations, temperature dependence, and sources of size-resolved PM components in Nanjing, east China.

Size-segregated ambient particulate matter (PM) samples were collected seasonally in suburban Nanjing of east China from 2016 to 2017 and chemically speciated. In both fine (< 2.1 µm, PM2.1) and coarse (> 2.1 µm, PM>2.1) PM, organic carbon (OC) accounted for the highest fractions (26.9% ± 10.9% and 23.1% ± 9.35%) of all measured species, and NO3- lead in average concentrations of water-soluble inorganic ions (WSIIs). The size distributions of measured components were parameterized using geometric mean diameter (GMD). GMD values of NO3-, Cl-, OC, and PM for the whole size range varied from < 2.1 µm in winter to > 2.1 µm in warm seasons, which was due to the fact that the size distributions of semi-volatile components (e.g., NH4NO3, NH4Cl, and OC) had a dependency on the ambient temperature. Unlike OC, elemental carbon (EC), and elements, NH4+, NO3-, and SO42- exhibited an increase trend in GMD values with relative humidity, indicating that the hygroscopic growth might also play a role in driving seasonal changes of PM size distributions. Positive matrix factorization was performed using compositional data of fine and coarse particles, respectively. The secondary formation of inorganic salts contributing to the majority (> 70%) of fine PM and 20.2% ± 19.9% of speciated coarse PM. The remaining coarse PM content was attributed to a variety of dust sources. Considering that coarse and fine PM had comparable mass concentrations, more attention should be paid to local dust emissions in future air quality plans.

The Number of Lymph Nodes Examined is Associated with Survival Outcomes of Neuroendocrine Tumors of the Jejunum and Ileum (siNET): Development and Validation of a Prognostic Model Based on SEER Database.

PURPOSE: The number of neuroendocrine tumors (NETs) is gradually increasing worldwide, and those located in the small intestine (siNETs) are the most common. As some biological and clinical characteristics of tumors of the jejunum and the ileum differ, there is a need to assess the prognosis of individuals with siNETs of the jejunum and ileum separately. We generated a predictive nomogram by assessing individuals with siNETs from the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: We used univariate Cox regression analysis to determine both the overall survival (OS) and the cancer-specific survival (CSS) of 2501 patients with a pathological confirmation of siNETs of the jejunum and ileum. To predict 3-, 5-, and 10-year OS of siNETs, a nomogram was generated based on a training cohort and validated with an external cohort. Accuracy and clinical practicability were evaluated separately by Harrell's C-indices, calibration plots, and decision curves. The correlation was examined between dissected lymph nodes and positive lymph nodes. RESULTS: Dissection of 7 or more lymph nodes significantly improved patient OS and was found to be a protective factor for patients with siNETs. In Cox regression analyses, age, primary site, tumor size, N stage, M stage, and regional lymph node examination were significant predictors in the nomogram. A significant positive correlation was found between dissected lymph nodes and positive lymph nodes. CONCLUSIONS: Patients with 7 or more dissected lymph nodes showed an accurate tumor stage and a better prognosis. Our nomogram accurately predicted the OS of patients with siNETs.

[Multi-omics analysis of regulating effects of hyperoside on lipid metabolism in high-fat diet mice].

The aim of this study was to explore the regulating effects of hyperoside (Hyp) on lipid metabolism in high-fat diet mice. The high-fat diet mouse model was established by high-fat diet induction. After 5 weeks of Hyp intragastric administration in high-fat diet mice, the serum lipid levels before and after Hyp administration were measured by the corresponding kits. The tissue structure of mouse liver was observed by HE staining before and after Hyp administration. The changes of intestinal flora and transcriptome were measured by Illumina platforms. Liquid chromatography-mass spectrometry (LC-MS) was used to determine non-targeted metabolites. The results showed that Hyp significantly reduced lipid levels in the high-fat diet mice and effectively restored the external morphology and internal structure of liver tissue. Hyp changed the species composition of the intestinal flora in high-fat diet mice, increased the abundance of beneficial flora such as Ruminococcus, and decreased the abundance of harmful flora such as Sutterella. Combined multi-omics analysis revealed that the effect of retinoic acid on lipid metabolism was significant in the high-fat diet mice treated with Hyp, while the increase of retinoic acid content was significantly negatively correlated with the expression of genes such as cyp1a2 and ugt1a6b, positively correlated with AF12 abundance, and significantly negatively correlated with unidentified_Desulfovibrionaceae abundance. These results suggest that Hyp may modulate the abundance of AF12, unidentified_Desulfovibrionaceae and inhibit the expression of genes such as cyp1a2 and ugt1a6b, thus increasing the content of retinoic acid and regulating lipid metabolism in the high-fat diet mice.

[Continuous PM2.5 Composition Measurements for Source Apportionment During Air Pollution Events].

To explore the application of high-temporal-resolution data in PM2.5 source apportionment during air pollution events, ambient air PM2.5 components were continuously monitored in urban Nanjing from January to December, 2017. Commercially available instruments for continuous measurements were deployed to obtain hourly concentrations of elements, water-soluble ions, and carbonaceous components of PM2.5. Data for 15 elements and 5 bulk components during three pollution events(firework combustion during the Spring Festival, a spring sandstorm, and a winter haze event) and across the whole year comprised four datasets for source apportionment using positive matrix factorization(PMF), and the distribution of factor/source contributions and estimations of average concentrations of characteristic components were compared based on different input datasets(PMFfirework-sand-haze and PMFfull-year). The results showed that the identified factors/sources, factor profiles, and contributions differed largely between PMFfirework-sand-haze and PMFfull-year solutions. For example, the relative average contribution of the firework combustion factor derived from the PMFfull-year solution(was 1.50%) was far less than that of the PMFfirework solution. The dust factor had an average contribution of 8.51% in the PMFsand solution, which was approximately double that of the PMFfull-year solution. This might be explained by the fact that PMF assumes unvaried source compositions during the measurement campaign, meaning that the source apportionment results based on long-term observations will include bias due to changes in emission sources. Furthermore, during the firework combustion event, the estimated average concentration of K from the PMFfirework solution[(1.32±1.17) µg·m-3, P=0.64]was closer to measured value[(1.36±1.19) µg·m-3]than that of the PMFfull-year solution[(1.16±1.19) µg·m-3, P=0.0090]. For the sand storm event, the concentrations of Fe, Si, and Ti were significantly underestimated by the PMFfull-year solution[(0.061±0.042)-(1.06±0.65) µg·m-3, P<0.05], while their peak concentrations agreed well between the PMFsand estimations and the observations. During the winter haze event, all PM2.5 bulk components were well estimated by both the PMFfull-year and PMFhaze solutions. Based on these results, PMF source apportionment results based on continuous measurement data during pollution events can reasonably reflect short-term variations in characteristic PM2.5 components and their sources, which can improve the timeliness of air pollution source apportionment.

Sensitivity of PM2.5 and O3 pollution episodes to meteorological factors over the North China Plain.

The Comprehensive Air-quality Model with extensions (CAMx) was used to explore the sensitivity of PM2.5 and O3 concentrations to four selected meteorological factors: wind speed, temperature, water vapor mixing ratio (Q), and planetary boundary layer height (PBLH) during two pollution episodes over the North China Plain (NCP). We also investigated the impact pathways of different meteorological factors on the formation of PM2.5 and O3. It is found that PM2.5 was more sensitive to the selected meteorological factors in the southeastern NCP, where high anthropogenic emissions and severe air pollution occur. Large variations were observed along the Taihang Mountains, where the height of the terrain changes dramatically. The sensitivity of O3 to wind speed, PBLH, temperature, and Q was mainly determined by the inhibition effects of PM2.5 in winter, while in summer, the complex chemical reactions were dominant. Significant diurnal variations of process analysis (PA) results were observed under various meteorological conditions. Higher temperature generally enhance heterogeneous chemistry and transport of NO3- through the top boundary layer during night-time in winter, however, in summer, the heterogeneous chemistry of NO3- and NH4+ during daytime were the major pathways to the increased PM2.5 due to increased temperature. Moreover, temperature alter PM2.5 concentrations through affecting vertical diffusivity and relative humidity, and alter O3 concentrations by affecting the gas phase chemistry and mass fluxes through the top boundary layer. Q mainly affects the rate of chemical reactions of PM2.5 and O3. The different impact pathways suggest that it is essential to consider variations in meteorological factors, in addition to the direct impacts of wind speed and PBLH, more attention should be paid to the complex impacts of temperature and Q, when developing emission control strategies.

Responses in PM2.5 and its chemical components to typical unfavorable meteorological events in the suburban area of Tianjin, China.

Air pollution is the result of enormous emissions and unfavorable meteorological conditions. The role of meteorology, particularly extremely unfavorable meteorological events (EUMEs), in processing atmospheric PM2.5 pollution has not been fully addressed. This work examined the variations of PM2.5 mass and its chemical components associated with various meteorological parameters and three EUMEs based on meteorological observations and analysis combined with one-year long in situ measurement in 2018 in the suburban area of Tianjin, China. Analysis shows that the polluted days in 2018 were mostly related to the increase in sulfate, nitrate, and ammonium (SNA). Temperature between -2 to 13 °C is more favorable for the formation of SNA, while high temperature exceeding 28 °C is favorable for the formation of organic carbon and sulfate. Most of the ions and carbon components showed significant increase in concentrations when relative humidity exceeded 80%. The maximum decreasing rate of PM2.5 concentrations due to increase in wind speed and planetary boundary height could be 15.35 µg m-3 (m s-1)-1, and 34.37 µg m-3 (100 m)-1, respectively. EUMEs showed significant impacts on PM2.5 components, in which PM2.5 concentrations showed the most significant increase under temperature inversion (TI) events, and surface-based TI (SBTI) events usually have much stronger impacts on PM2.5 concentrations than elevated TI (ELTI). Nitrate was found to be the most sensitive component to EUMEs, especially under multiple EUMEs. The synthetic effects of multiple EUMEs could result in an increase of nitrate by 35.53 µg m-3 (523.3%). In addition, OC and sulfate are more sensitive to heat wave events. Our analysis provides improved understanding of the formation of PM2.5 pollution with respect to meteorology, particularly EUMEs. Based on such information, more attention may be needed on the collaborative prediction of EUMEs and air pollution episodes.

The complex roles of neutrophils in APAP-induced liver injury.

Acetaminophen (APAP) is a widely applied drug for the alleviation of pain and fever, which is also a dose-depedent toxin. APAP-induced acute liver injury has become one of the primary causes of liver failure which is an increasingly serious threat to human health. Neutrophils are the major immune cells in human serving as the first barrier against the invasion of pathogen. It has been reported that neutrophils patriciate in the occurrence and development of APAP-induced liver injury. However, evolving evidences suggest that neutrophils also contribute to tissue repair and actively orchestrate resolution of inflammation. Here, we addressed the complex roles in APAP-induced liver injury on the basis of brief introduction of neutrophil's activation, recruitment and migration.

Neutrophil: An emerging player in the occurrence and progression of metabolic associated fatty liver disease.

Metabolic-associated fatty liver disease (MAFLD) is a common type of chronic liver disease characterized by excessive lipid accumulation in hepatocytes, but the pathogenesis is still unclear. Neutrophils, the most abundant immune cells in the human body, defend against pathogens and regulate the inflammatory response. Recent studies have indicated that excessive liver infiltration of neutrophils is a significant histological hallmark of MAFLD, and neutrophils and their derived granule proteins participate in different stages of MAFLD, including hepatic steatosis, inflammation, fibrosis, cirrhosis and hepatocellular carcinoma. Hence, in this review, we summarize the role of neutrophils in the occurrence and progression of MAFLD and provide a perspective for the clinical application of neutrophils in MAFLD diagnosis and treatment.

[Light-absorbing Properties and Sources of PM2.5 Organic Components at a Suburban Site in Northern Nanjing].

The light absorption of organic components in PM2.5 was investigated at a suburban site in northern Nanjing from September 2018 to September 2019, and PM2.5 compositional data and principal component analysis (PCA) were used to identify the sources of light-absorbing organic carbon (brown carbon, BrC). The results showed that the average light absorption coefficients of water-soluble organic carbon (WSOC) and methanol extractable organic carbon (MEOC) were (3.22±2.18) Mm-1 (Abs365,w) and (7.69±4.93) Mm-1(Abs365,m), respectively. Significant correlations were observed between Abs365,w and mass concentrations of WSOC (r=0.72, P<0.01) and between Abs365,m and mass concentrations of MEOC (r=0.62, P=0.04). Both Abs365,w and Abs365,m exhibited seasonal variations, with higher values during winter than during summer,and higher diel variations at night than during the day. This can be attributed to meteorological characteristics during the winter and nighttime, i.e., decreased boundary layer height and increased atmospheric stability, enhanced primary emissions in winter,and stronger photobleaching effects during the summer and during the day. The annual average Abs365,m/Abs365,w ratio (2.60±0.92) was much larger than the average mass ratio of MEOC/WSOC (1.37±0.30), indicating that the water-insoluble fraction of MEOC had a stronger light absorption effect and dominated BrC absorption. No strong correlation (r<0.60) was observed between WSOC, MEOC, Abs365,m, and mass concentrations of K+, indication that biomass burning was not the main source of BrC in the study location. The mass absorption efficiency of WSOC (MAE365,w) and MEOC (MAE365,m) and their ratios (MAE365,m/MAE365,w) showed similar seasonal variations to Abs365. The average MAE365 value of the water-insoluble fraction of MEOC (4.10±5.15) m2·g-1 was 6.0 and 2.9 times higher than that of MAE365,w and MAE365,m, respectively, suggested that BrC absorption was primarily attributable to water-insoluble components. In comparison to the absorption Ångström exponent of WSOC (ÅWSOC), ÅMEOC displayed marked temporal variability, which might be related to the seasonal variation in the emission of water-insoluble chromophores. According to the PCA results, the light absorption of PM2.5 organic was mainly attributed to secondary formation and anthropogenic primary emissions rather than biomass burning.

Neddylation inhibitor MLN4924 has anti-HBV activity via modulating the ERK-HNF1α-C/EBPα-HNF4α axis.

Hepatitis B virus (HBV) infection is a major public health problem. The high levels of HBV DNA and HBsAg are positively associated with the development of secondary liver diseases, including hepatocellular carcinoma (HCC). Current treatment with nucleos(t)ide analogues mainly reduces viral DNA, but has minimal, if any, inhibitory effect on the viral antigen. Although IFN reduces both HBV DNA and HBsAg, the serious associated side effects limit its use in clinic. Thus, there is an urgent demanding for novel anti-HBV therapy. In our study, viral parameters were determined in the supernatant of HepG2.2.15 cells, HBV-expressing Huh7 and HepG2 cells which transfected with HBV plasmids and in the serum of HBV mouse models with hydrodynamic injection of pAAV-HBV1.2 plasmid. RT-qPCR and Southern blot were performed to detect 35kb mRNA and cccDNA. RT-qPCR, Luciferase assay and Western blot were used to determine anti-HBV effects of MLN4924 and the underlying mechanisms. We found that treatment with MLN4924, the first-in-class neddylation inhibitor currently in several phase II clinical trials for anti-cancer application, effectively suppressed production of HBV DNA, HBsAg, 3.5kb HBV RNA as well as cccDNA. Mechanistically, MLN4924 blocks cullin neddylation and activates ERK to suppress the expression of several transcription factors required for HBV replication, including HNF1α, C/EBPα and HNF4α, leading to an effective blockage in the production of cccDNA and HBV antigen. Our study revealed that neddylation inhibitor MLN4924 has impressive anti-HBV activity by inhibiting HBV replication, thus providing sound rationale for future MLN4924 clinical trial as a novel anti-HBV therapy.